Abstract. ?Challenging? HIV-infected patients, those not retained in treatment, represent a critical focus for positive prevention, as retention in care is also associated with reduction in overall community-level viral burden. Linkage to care, early initiation of antiretroviral therapy (ART), adherence and retention in treatment enables HIV-infected individuals to achieve and maintain viral suppression to non-detectable levels, optimizing health and reducing HIV transmission. Argentina was one of the first Latin American countries to guarantee HIV prevention, diagnosis and comprehensive care services, including antiretroviral (ARV) medication, which removed cost and access as barriers to care for HIV-infected patients. Yet, as in the USA, drop out occurs at every stage of the HIV continuum. An estimated 110,000 individuals are HIV-infected in Argentina; of these, 77,000 (70%) have been diagnosed and 60,000 (54%) were linked to care. However, only 36% have achieved viral suppression and 31% of those diagnosed delayed entry to care. Our pilot study estimated retention in care ranged from 65-90%. Given universal access to care, patients with uncontrolled HIV constitute an urgent public health problem due to the increased likelihood of viral resistance, treatment failure and HIV transmission. To achieve meaningful reductions in HIV infection at the community level, new and innovative strategies must be developed to re-engage patients not retained in care. Motivational Interviewing (MI) is a widely used collaborative patient-centered approach and has been used by therapists in Central and South America to enhance motivation and commitment in substance use and risk reduction. Our recently completed pilot feasibility study targeted challenging patients not retained in treatment in public and private clinics in Buenos Aires, Argentina. The pilot study, which utilized MI and was culturally tailored to the local setting, was feasible and acceptable to patients, physicians and clinic staff. Results demonstrated that a physician-based MI intervention was effective in re-engaging patients in care, i.e., enhanced and sustained patient adherence, viral suppression and patient-physician communication and attitudes about treatment among these patients at 6 and 9 months post baseline. The proposed clinical trial seeks to extend these findings in public and private clinics in 4 urban population centers in Argentina, in which clinics (N = 6 clinics, 6 MDs per site) are randomized to experimental (physician MI Intervention) (n = 3) or control (physician Standard of Care) (n = 3) conditions in a 3:3 ratio. Using a cluster randomized clinical trial design, the proposed study will test the effectiveness of a physician-based Motivational Interviewing intervention to improve and sustain retention, adherence, persistence and viral suppression among ?challenging? patients (n = 360) over 24 months. Results will have important public health implications for the implementation of MI to re-engage and retain patients in HIV treatment and care and improve viral suppression through high levels of medication adherence.